The present invention relates to the preparation, from aniline derivatives, of indole carboxylic acid derivatives which are useful as intermediate products in the pharmaceutical industry.
Indole carboxylic acid derivatives may be used as intermediate products in preparing pharmaceutically usable active substances. For instance, indole carboxylic acid derivatives can be reacted with bicyclic alkaloid radicals having an 8-azabicyclo-[3,2,1]-octane type of structure, for example with tropine or with 3-amino-8-methyl-8-azabicyclo-[3,2,1]octane, to yield pharmacologically active substances having 5-HT.sub.3 -antagonistic properties, which are suitable for the treatment of serotonin-induced gastrointestinal complaints (see European Patent No. 0 189 002 A2). In particular, pharmacologically active substances which can be obtained from 1,7-fused indole carboxylic acid derivatives and the aforementioned bicyclic alkaloid radicals are strong and selective antagonists of neuronal 5 HT receptors, which are useful in treating complaints induced by overstimulation of these receptors (see European Patent No. 0 322 016 A1). Pharmacologically active substances with CCK-antagonistic properties can be obtained by reacting 1,7-fused 1H-indole-2-carboxylic acid derivatives with 3-amino-1,4-benzodiazepine derivatives.
Indole carboxylic acid derivatives may, inter alia. be prepared by reacting phenylhydrazine derivatives with pyruvic acid derivatives. The phenylhydrazine derivatives required for this purpose must themselves be obtained from corresponding phenylnitrosamine derivatives. The latter are produced by nitration of aniline derivatives.